September 13, 2012

Systemic Lupus Erythematosus

Systemic Lupus Erythematosus (SLE) can also be referred to as Lupus. It is a long-term disease involving the immune system that may affect the skin, joints, kidneys, brain, and other organs causing many varied symptoms, the most common being tiredness, joint pains and skin rashes. In its severe form, problems of the kidneys and other organs occur. Anti-inflammatory pain killers are often used for the joint pains. Steroids and other medications are required for its severe form.

In this article:
What is lupus?
Risk factors and causes
Clinical features
Investigations
Diagnosis
Complications
Treatment
Monitoring SLE and the future of the disease

What is lupus?

Lupus is a persistent (or chronic) disease that causes inflammation in various parts of the body because the immune system attacks the body’s own cells and tissue (autoimmune disease), resulting in a continuous inflammatory response and tissue damage. The severity of lupus ranges from mild to severe.

There are two main forms of lupus. Discoid lupus only affects the skin. It is not discussed in this article. The other form is systemic lupus (also Systemic Lupus Erythematosus [SLE]), which primarily affects the connective tissue. Because it primarily involves the connective tissue, multiple organ systems, including the skin, joints, kidneys, lungs, nervous system, serous membranes, and/or other organs of the body are affected as well. This article is about Systemic Lupus Erythematosus (SLE).

Risk factors and causes

Systemic lupus erythematosus is more common, and more severe, in nonwhite patients. African Americans and Asians are affected more often than people from other races. The highest prevalence among ethnic groups is in blacks.

SLE is much more common in women than men. SLE is up to 10 times more common in women than in men and typically occurs during child-bearing age. It may occur at any age, but appears most often in people between the ages of 10 and 50 (some medical literature have peak age of onset between 15 and 45 years).

SLE may also be caused by certain drugs. Estrogen may play a role in the pathophysiology of SLE, but this has not yet been proven conclusively. Women exposed to estrogen-containing oral contraceptive pills (OCPs), however, do have an increased risk of developing SLE, especially if they started using them recently.

Is lupus hereditary?

Although lupus can run in families, only around 3 in 100 children of people with lupus will actually develop the disease. Even in identical twins, if one twin has lupus the other only has a 1 in 4 chance of developing it too. So even though there is some hereditary factor, it is clear that other factors are involved in whether a person develops lupus or not.

What causes lupus?

Lupus is an autoimmune disease. This means that the immune system (which normally protects the body from infections) mistakenly attacks healthy cells. This can cause symptoms and may damage the affected parts of the body. Other autoimmune diseases include diabetes, rheumatoid arthritis and thyroid disorders.

It is not known why lupus occurs. Possible triggers of lupus include infections, medicines (for example, minocycline or hydralazine) or sunlight. Hormonal changes may play a role in lupus, which could explain why it is much more common in women.

Clinical features

Systemic lupus erythematosus (SLE) is characterized by a wide spectrum of signs and symptoms due to the ongoing presence of a variety of antigens, auto-antibodies, and immune complexes, which result in accumulated tissue damage to the point of clinical manifestation. Thus, symptoms vary from person to person, and may come and go (remitting and relapsing), with a variety of different presentations. The disease course is as variable as it is unpredictable, with periods of illness, or "flares," alternating with periods of remission.

The American College of Rheumatology (ACR) diagnostic criteria for lupus includes 11 manifestations. These criteria include:
  1. Serositis (pleuritis, pericarditis)
  2. Oral ulcers
  3. Arthritis (nonerosive)
  4. Photosensitivity (exposure to UV radiation causes skin manifestations)
  5. Blood dyscrasias (hemolytic anemia, leukopenia, thrombocytopenia)
  6. Renal manifestations (proteinuria, casts)
  7. Positive ANA finding
  8. Immunologic disorders (anti-Smith antibodies positive, antiphospholipid antibody positive, false positive test for syphilis, presence of anti–double-stranded DNA antibodies)
  9. Neurologic manifestations (seizures, focal signs, psychosis)
  10. Butterfly (or, malar) rash. See image below.
  11. Discoid rash
Malar rash of Systemic Lupus Erythematosus
The butterfly rash of lupus. Image credit: Doktorinternet / CC BY-SA
Systemic lupus erythematosus (SLE) is a true multisystem disease affecting many organs and body systems, however, at least 4 out of the above-listed 11 typical features must be present for a diagnosis of SLE.

Common signs and symptoms of systemic lupus erythematosus
Common signs and symptoms of systemic lupus erythematosus.
By Mikael Häggström, used with permission (public domain)

Investigations

SLE is a multisystem autoimmune disorder. The diagnosis requires a combination of clinical features and the presence of at least one relevant immunological abnormality. If there is a clinical suspicion of lupus, blood tests including serological markers should be checked.

When SLE is suspected, useful screening investigations are urinalysis, full blood count (FBC), erythrocyte sedimentation rate (ESR) or plasma viscosity and antinuclear factor.
  • Urinalysis: as initial test for proteinuria/haematuria.
  • FBC and ESR:
    • Mild normochromic normocytic anaemia is common. Anaemia in patients with lupus may be drug-induced or due to chronic disease, but it is sometimes due to haemolytic anaemia. In this case, Coombs' antibody, reticulocyte count and haptoglobins may need to be checked.
    • Leukopenia and thrombocytopenia occur frequently but can also be due to immunosuppressive therapy.
    • ESR is raised but CRP may be normal unless there is intercurrent infection or serositis.
Serology:
  • Antinuclear antibodies (ANAs) are present in about 95% of SLE patients. If the test is negative, there is a low clinical probability of the patient having SLE. A positive ANA occurs in approximately 5% of the adult population and alone has poor diagnostic value in the absence of clinical features of autoimmune rheumatic disease.
  • The presence of anti-double stranded DNA (anti-dsDNA) antibodies, low complement levels or anti-Smith (Sm) antibodies are highly predictive of a diagnosis of SLE in patients with relevant clinical features. Anti-Ro/La and anti-RNP antibodies are less specific markers of SLE as they are found in other autoimmune rheumatic disorders as well as SLE.
  • Antiphospholipid antibodies should be tested in all lupus patients at baseline, especially in those with an adverse pregnancy history or arterial/venous thrombotic events. Confirmatory tests for antiphospholipid syndrome are positive lupus anticoagulant, anti-cardiolipin antibodies (IgG, IgM) and/or anti-beta-2 glycoprotein-1 (IgG, IgM) on two occasions at least 12 weeks apart.
Other investigations will depend on system involvement - eg, MRI brain scan, echocardiogram, renal biopsy.

Women with SLE are at greatly increased risk of premature atherosclerosis and the risk is independent of established cardiovascular risk factors. Monitoring for all cardiovascular risk factors is therefore essential.

Diagnosis

The presence of 4 or more of the ACR criteria as listed above, either serially or simultaneously, is diagnostic of SLE. About 80% of patients have skin involvement manifesting as photosensitivity, malar (butterfly) and discoid rash (thick, red, scaly patches on the skin), ulcers in the oral and nasal cavities or in the vagina, or alopecia, all of which are part of ACR diagnostic criteria. However, an absence of skin manifestation, should not lower clinical suspicion for lupus because its symptoms vary and come and go unpredictably. Diagnosing SLE can thus be elusive, with some patients suffering from unexplained symptoms of untreated SLE for years, such as the initial (and chronic) complaints of fever, malaise, joint pains, myalgias, and fatigue, as well as temporary loss of cognitive abilities.

When SLE is diagnosed, it is important to establish the severity and potential reversibility of the illness in order to institute appropriate therapy. Treatment options usually focus on the suppression of symptoms rather than treating the cause, since there is not an actual "cure" for the disease.

Complications

Renal disease remains the most serious complication of SLE. It affects 30%-60% of patients. Renal involvement is characterized by proteinuria (> 0.5 g/24h) and/or active urinary sediment (> 5 red blood cells per high-power field, pyuria, or cell casts). In patients with inactive sediment and > 500 mg/day of proteinuria, monitoring is recommended with urinalysis every 3-6 months for 3 years; every 3 months is preferred in patients with anti–double-stranded DNA antibodies and/or hypocomplementemia.

Prompt renal biopsy is required in all lupus patients with evidence of kidney involvement to determine the histologic subtype of lupus nephritis. The typical histologic picture is of a membranous glomerulonephritis, with "wire-loop" abnormalities that result from the granular appearance (on immunohistochemical staining) of immune-complex deposition along the glomerular basement membrane. The World Health Organization (WHO) classification of glomerulonephritis in SLE includes grades I to VI. Pathology reports also reflect the extent of inflammatory (reversible) and chronic (irreversible scarring) changes. In general, treatment for lupus nephritis is not recommended in patients with class I or II disease or in those with extensive irreversible changes. In contrast, aggressive immunosuppression is recommended for patients with disease class III, IV, or V with inflammatory proliferative lesions, because a majority of those individuals, if untreated, develop end-stage renal disease (ESRD). However, ESRD is seen in fewer than 5% of SLE cases, due to earlier detection and subsequent prompt management of the disease. Lupus nephritis tends to be an ongoing disease, with flares often requiring repeat biopsy and repeated treatment over time.

Pleural inflammation is a common feature of SLE and is the most common pulmonary manifestation of SLE. It causes chest pain, shortness of breath, and cough. Pleural effusions are typical findings and are usually ANA-positive exudates with low complement. Less frequent pulmonary complications of SLE include interstitial lung disease and pulmonary hypertension.

The most common hematologic manifestation of SLE is anemia, usually normochromic normocytic, which is often overlooked in young menstruating women. Iron deficiency may also develop. Leukopenia and thrombocytopenia are common as well, which may be due to the primary disease process or may be a side effect of the subsequent pharmacologic treatment for the disease. Leukopenia almost always consists of lymphopenia, not granulocytopenia. Patients with SLE may also have signs and symptoms of a thrombotic disorder known as antiphospholipid syndrome, wherein autoantibodies to phospholipids are present in the serum. Serum levels of anticardiolipin antibodies should also be checked in patients suspected of having SLE. The presence of these antibodies may result in a false positive test for syphilis. Lymphadenopathy is not an uncommon presentation in SLE; it occurs in 15%-26% of patients. However, diffuse lymphadenopathy is very rare and is reported in very few cases. It is not one of the ACR criteria for the diagnosis of SLE. Lymph node biopsy may be warranted to exclude alternative diagnoses. The patient in this case underwent lymph node biopsy, which showed no evidence of lymphoproliferative disorder.

Read this interesting case challenge of a 41 year old woman presenting with breathlessness, blood in urine and enlarged lymph nodes.

Treatment

There is no cure for SLE. Treatment of SLE is aimed at controlling acute flares and using maintenance strategies that suppress symptoms to an acceptable level, while preventing further organ damage.

For milder manifestations of SLE, such as arthritis, dermatitis, and constitutional symptoms, nonsteroidal anti-inflammatory medications (NSAIDs), hydroxychloroquine, and low-dose steroids have been used with success. Corticosteroid creams may be used for skin rashes.

Severe forms of the disease, including those with more life-threatening courses (including lupus nephritis, hemolytic anemia, extensive heart or lung involvement, kidney disease, or central nervous system involvement), require a combination therapy of high-dose systemic glucocorticoids and cyclophosphamide or mycophenolate mofetil to induce remission, followed by longer-term, intense immunosuppressive therapy to maintain response.

Protective clothing, sunglasses, and sunscreen are encouraged when in the sun. It is also important to have preventive heart care, up-to-date immunizations, and tests to screen for thinning of the bones (osteoporosis). Talk therapy and support groups may help relieve depression and mood changes that may occur in patients with this disease.

Monitoring SLE and the future of the disease

A number of research protocols (Systemic Lupus Activity Measure [SLAM], SLE Disease Activity Index [SLEDAI], etc) have been designed in order to accurately monitor disease activity, which all use combinations of history, physical examination findings, and laboratory data. Meanwhile, the search for reliable markers of disease activity continues. Complement activation products, soluble T-cell activation markers, antibodies to C1q, and the use of nucleosomes have been reported but not validated for universal clinical use. Currently, widely used indicators include anti–double-stranded DNA antibodies, complement levels, hemoglobin levels, platelet count, urine analysis, and serum levels of creatinine and albumin. Because there is great variability in SLE's presentation and course, predicting a flare in a particular patient should take into account laboratory findings that correlate with flares in the past.

Reference(s):
1). Medscape CME: A 41-Year-Old Woman With Shortness of Breath, Hematuria, and Lymphadenopathy. Available online: https://www.medscape.org/viewarticle/727945
2). Makover M.E, Zieve D (reviewers). Systemic lupus erythematosus. PubMed Health, U.S. National Library of Medicine. Accessed 13.09.2012. Available here: http://www.ncbi.nlm.nih.gov/pubmedhealth/PMH0001471/

No comments:

Post a comment

Got something to say? We appreciate your comments: